rs2070767

Variant names:

• chr22-23895276-T-C
• rs2070767
• ENST00000406213.1:n.626A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000406213.1(MIF-AS1):​n.626A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 802,300 control chromosomes in the GnomAD database, including 243,932 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.78 (46334 hom., cov: 30)
  • Exomes 𝑓: 0.78 (197598 hom.)
• Consequence: MIF-AS1 ENST00000406213.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.309
• Publications: 21 publications found

Genes affected

MIF-AS1 (HGNC:27669): (MIF antisense RNA 1)

ENSG00000290199 (HGNC:):

MIF (HGNC:7097): (macrophage migration inhibitory factor) This gene encodes a lymphokine involved in cell-mediated immunity, immunoregulation, and inflammation. It plays a role in the regulation of macrophage function in host defense through the suppression of anti-inflammatory effects of glucocorticoids. This lymphokine and the JAB1 protein form a complex in the cytosol near the peripheral plasma membrane, which may indicate an additional role in integrin signaling pathways. [provided by RefSeq, Jul 2008]

MIF Gene-Disease associations (from GenCC):

• cystic fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.022).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000406213.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIF-AS1	NR_038911.1		n.626A>G		non_coding_transcript_exon	Exon 3 of 3
	MIF	NM_002415.2	MANE Select	c.*170T>C		downstream_gene	N/A	NP_002406.1	P14174

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIF-AS1	ENST00000406213.1	TSL:1	n.626A>G		non_coding_transcript_exon	Exon 3 of 3
	ENSG00000290199	ENST00000703580.1		n.1221A>G		non_coding_transcript_exon	Exon 4 of 4
	ENSG00000290199	ENST00000717616.1		n.213-3810A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118618 AN: 151868 Hom.: 46290 Cov.: 30

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.793

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.804

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.768

GnomAD2 exomes AF: 0.784 AC: 115256 AN: 146996 AF XY: 0.784

Gnomad AFR exome AF: 0.789

Gnomad AMR exome AF: 0.810

Gnomad ASJ exome AF: 0.744

Gnomad EAS exome AF: 0.672

Gnomad FIN exome AF: 0.807

Gnomad NFE exome AF: 0.778

Gnomad OTH exome AF: 0.794

GnomAD4 exome AF: 0.778 AC: 505886 AN: 650314 Hom.: 197598 Cov.: 8 AF XY: 0.779 AC XY: 269411 AN XY: 345700

African (AFR) AF: 0.792 AC: 13730 AN: 17340

American (AMR) AF: 0.808 AC: 28096 AN: 34780

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 15209 AN: 20510

East Asian (EAS) AF: 0.658 AC: 21320 AN: 32410

South Asian (SAS) AF: 0.821 AC: 52349 AN: 63748

European-Finnish (FIN) AF: 0.806 AC: 38513 AN: 47778

Middle Eastern (MID) AF: 0.800 AC: 3400 AN: 4248

European-Non Finnish (NFE) AF: 0.776 AC: 307166 AN: 396000

Other (OTH) AF: 0.779 AC: 26103 AN: 33500

GnomAD4 genome AF: 0.781 AC: 118716 AN: 151986 Hom.: 46334 Cov.: 30 AF XY: 0.784 AC XY: 58229 AN XY: 74296

African (AFR) AF: 0.788 AC: 32654 AN: 41456

American (AMR) AF: 0.793 AC: 12128 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.758 AC: 2631 AN: 3470

East Asian (EAS) AF: 0.673 AC: 3456 AN: 5136

South Asian (SAS) AF: 0.825 AC: 3974 AN: 4818

European-Finnish (FIN) AF: 0.804 AC: 8505 AN: 10578

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.776 AC: 52695 AN: 67934

Other (OTH) AF: 0.764 AC: 1606 AN: 2102

Alfa AF: 0.778 Hom.: 31226

Bravo AF: 0.781

Asia WGS AF: 0.758 AC: 2636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	8.1
DANN	Benign	0.46
PhyloP100		0.31

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2070767;

hg19: chr22-24237463;

COSMIC: COSV53158711;